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Genomes for the Curious

So jealous: Science journalist Eliza Strickland not only had her genome sequenced but she got to write a long feature about the experience. Her story just came out in IEEE Spectrum and I’d highly recommend giving it a read. It includes a mini-profile of Jonathan Rothberg, the CEO of DNA sequencing company Ion Torrent and one of the biggest names in genetics. But Strickland’s personal story is what really drives the narrative. (Spoiler alert: This post will mention highlights of her story, so go read it first if you want to be surprised.)

Strickland went to the commercial sequencing lab of Baylor College of Medicine in Houston. Doctors from all over the country have sent samples of their patients’ blood to Baylor for exome sequencing. (The exome includes all of the sections of the genome that code for proteins. It’s only a fraction of the whole genome, but the only part that scientists know how to interpret, for now). The test costs $7,000 and requires a doctor’s referral.

Strickland writes that she was Baylor’s first “merely curious” patient, meaning that she didn’t have anything wrong with her. She just wanted to look at her potential risks. Technically, she told me, she was referred by a doctor, Baylor’s own Jim Lupski, an MD/PhD. So does that mean Baylor is taking orders from the merely curious? Yep, pretty much. “If you had a family doctor who was on board with a curiosity-driven exome scan, you could get it done. I don’t believe Baylor would raise any objections,” she says.

In her story, Strickland describes how the whole process worked, including important conversations she had with her family before and after the test. Lupski and his team interpreted her results, creating a six-page report of all of the variants in her genome that might be medically relevant. (Baylor told her from the get-go that they wouldn’t be interpreting non-medical variants, such as hair or eye color.) Strickland carries several potentially scary genomic blips, such as those linked to Parkinson’s and kidney failure, but nothing that requires immediate action.

At first, she was disappointed that the findings weren’t more informative. But then she finds something interesting about Usher syndrome, a recessive disease that she’s a carrier for:

Then comes a surprise that casts doubt on my first judgment and forces me to see exome sequencing in a new light. In the weeks following my meeting at Baylor I idly Google the various conditions listed in the report the doctors gave me. One afternoon I type in “Usher syndrome” and follow a link to a National Institutes of Health Web page about the disorder. A few sentences in, I feel a shock of recognition. The syndrome, I read, is associated not just with deafness but also with night blindness and severe balance problems. My mother has been completely unable to see in the dark for as long as she can remember, and both she and her older brother have gotten dangerously wobbly on their feet over the past decade.

There are many bioethicists and researchers who would argue that this information isn’t worth knowing, either, because there is no treatment for Usher syndrome. I totally disagree with this stance (as I’ve argued elsewhere), and I think Strickland’s story shows why even ambiguous or “non-actionable” information can be powerful, assuming you want to hear about it. Strickland’s mother won’t benefit from a treatment, but she now has an explanation for otherwise mysterious symptoms. And if Strickland wanted to have children someday (I’m not sure if she does), her husband could be screened to see if he’s also an Usher carrier.

But most interesting to me is the power of genome scans to help everyday people better understand what their genes do and do not say about their future. As the costs come down, and more and more curious people have experiences like Strickland’s, I think (and hope) that our culture will gradually stop being afraid of the big bad genome. It’s a potentially useful medical tool, like a cholesterol test or cat scan, that may or may not lead to medical insights. But you can’t find out what it means unless you look.

9 thoughts on “Genomes for the Curious

  1. Thanks for giving the article such a thoughtful treatment, Ginny.

    I do agree that even just looking at one’s genome is a useful exercise– it was fascinating to be prodded to think about my medical future in this way. And the possible DOOOOOMs that I learned about will stick in my head for a long while, I expect.

  2. Hey Virginia: a question. What would Baylor have provided in the way of analysis, if her doctor had not been on board to write up a six-page report?

  3. Hi Laura, Ginny asked me to reply to your question.

    Baylor’s commercial lab provides the sequencing and analysis, so the 6-page report I got was part of the standard package. My report included 1) variants with previously reported associations with adult-onset diseases, 2) mutations in genes causing recessive Mendelian disorders, 3) some pharmacogenetic results, and finally 4) a long list of variants of “unknown clinical significance” in genes associated with cancer and adult-onset diseases.

    However, I was an extremely unusual case, in that I was a presumably healthy individual with no pressing medical concerns. In most cases, patients get sequenced because they’re experiencing a medical problem, or they have a family history of some problem. These patients receive reports that are much more focused on the relevant genetic information.

  4. I am the Chairman of the Coalition for Usher Syndrome Research (http://www.usher-syndrome.org) i would strongly encourage anyone with suspected Usher syndrome to confirm it via genetic testing. While there are few widely accepted treatments available today, there are a number of treatments reaching clinical trial that hold tremendous promise. Usher syndrome is not a death sentence. People with Usher live happy productive lives. There are tests available today that are covered by insurance that can identify all known Usher syndrome mutations. Please feel free to contact me if you’d like any more information about the tests or the disease.

  5. It certainly seems like an interesting result that her mother and uncle had signs of Usher’s when they were presumably heterozygous for the mutation(s). Or is it known to be a condition where haploinsufficiency is the norm?

  6. Have you heard of 23andme.com? You can get similar results (and cool things like your ancestry and neanderthal ancestry) for $99. I have my sample submitted- waiting on results!

  7. Hi Virginia,
    It is a thoughtful and nice treatment to an experience as a curious individual on genomics. I have a different experience about the whole genome project when it was first conceived way back in early 1980s and a student of statistics, I was studying genetics and the follow up on many things which materialised towards the beginning of 21st century in the form of genographic project. I just wanted to confirm my belief that all the people have one common ancestor on the paternal line of which results have come to a large extent. I was very happy to note that sitting in Kashmir (India), I share a common haplogroup with a person, whose body was found about 12 years back on the bio-diversity park close to Washington DC and this person had died almost 9100 years back. It is beautiful for a persons to connect with the whole lot of population across the globe. Let us see what happens in the second stage of genographic project when we can sequence the maternal line of individuals when we know that 95 percent population share a common ancestor about 70,000 years back and all the people on earth have one ancestor about 140,000 years back. Let us find the common mother and be blessed to make this world better place to live for others.
    I am working as a journalist for 30 years and heading an organisation Kashmir Times Publications http://www.kashmirtimes.com.
    Thanks and regards for providing new insights in the world of science.
    Prabodh Jamwal

  8. “It’s only a fraction of the whole genome, but the only part that scientists know how to interpret, for now.”

    That’s a bit of a misstatement. The reason we do exome (WES) over whole genome sequencing (WGS) is mostly because of cost. WGS costs 6x as much as WES. As reagent costs decrease, so will the use of WES over WGS. The other reason we do WES is because the vast majority of inherited genetic disorders occur in protein coding regions. The sequencing data from WGS provides more variants, but many of those variants are not clinically relevant because they occur in regions that do not directly affect genes or gene expression.

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